Laboratory-acquired infections and pathogen escapes worldwide between 2000 and 2021: a scoping review.

Laboratory-acquired infections (LAIs) and accidental pathogen escape from laboratory settings (APELS) are major concerns for the community. A risk-based approach for pathogen research management within a standard biosafety management framework is recommended but is challenging due to reasons such as inconsistency in risk tolerance and perception. Here, we performed a scoping review using publicly available, peer-reviewed journal and media reports of LAIs and instances of APELS between 2000 and 2021. We identified LAIs in 309 individuals in 94 reports for 51 pathogens. Eight fatalities (2·6% of all LAIs) were caused by infection with Neisseria meningitidis (n=3, 37·5%), Yersinia pestis (n=2, 25%), Salmonella enterica serotype Typhimurium (S Typhimurium; n=1, 12·5%), or Ebola virus (n=1, 12·5%) or were due to bovine spongiform encephalopathy (n=1, 12·5%). The top five LAI pathogens were S Typhimurium (n=154, 49·8%), Salmonella enteritidis (n=21, 6·8%), vaccinia virus (n=13, 4·2%), Brucella spp (n=12, 3·9%), and Brucella melitensis (n=11, 3·6%). 16 APELS were reported, including those for Bacillus anthracis, SARS-CoV, and poliovirus (n=3 each, 18·8%); Brucella spp and foot and mouth disease virus (n=2 each, 12·5%); and variola virus, Burkholderia pseudomallei, and influenza virus H5N1 (n=1 each, 6·3%). Continual improvement in LAI and APELS management via their root cause analysis and thorough investigation of such incidents is essential to prevent future occurrences. The results are biased due to the reliance on publicly available information, which emphasises the need for formalised global LAIs and APELS reporting to better understand the frequency of and circumstances surrounding these incidents.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Foot and Mouth Disease Virus.

Introduction: Foot and mouth disease (FMD) is a highly contagious infection of cloven-hoofed animals. The Biosafety Research Road Map reviewed scientific literature regarding the foot and mouth disease virus (FMDV). This project aims to identify gaps in the data required to conduct evidence-based biorisk assessments, as described by Blacksell et al., and strengthen control measures appropriate for local and national laboratories. Methods: A literature search was conducted to identify potential gaps in biosafety and focused on five main sections: the route of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination strategies. Results: The available data regarding biosafety knowledge gaps and existing evidence have been collated. Some gaps include the need for more scientific data that identify the specific safety contribution of engineering controls, support requirements for showering out after in vitro laboratory work, and whether a 3- to 5-day quarantine period should be applied to individuals conducting in vitro versus in vivo work. Addressing these gaps will contribute to the remediation and improvement of biosafety and biosecurity systems when working with FMDV.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Crimean Congo Haemorrhagic Fever Virus and Lassa Virus.

Introduction: Crimean Congo Hemorrhagic Fever (CCHF) virus and Lassa virus (LASV) are zoonotic agents regarded as high-consequence pathogens due to their high case fatality rates. CCHF virus is a vector-borne disease and is transmitted by tick bites. Lassa virus is spread via aerosolization of dried rat urine, ingesting infected rats, and direct contact with or consuming food and water contaminated with rat excreta. Methods: The scientific literature for biosafety practices has been reviewed for both these two agents to assess the evidence base and biosafety-related knowledge gaps. The review focused on five main areas, including the route of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination strategies. Results: There is a lack of data on the safe collection and handling procedures for tick specimens and the infectious dose from an infective tick bite for CCHF investigations. In addition, there are gaps in knowledge about gastrointestinal and contact infectious doses for Lassa virus, sample handling and transport procedures outside of infectious disease areas, and the contribution of asymptomatic carriers in viral circulation. Conclusion: Due to the additional laboratory hazards posed by these two agents, the authors recommend developing protocols that work effectively and safely in highly specialized laboratories in non-endemic regions and a laboratory with limited resources in endemic areas.

Developing One Health surveillance systems.

The health of humans, domestic and wild animals, plants, and the environment are inter-dependent. Global anthropogenic change is a key driver of disease emergence and spread and leads to biodiversity loss and ecosystem function degradation, which are themselves drivers of disease emergence. Pathogen spill-over events and subsequent disease outbreaks, including pandemics, in humans, animals and plants may arise when factors driving disease emergence and spread converge. One Health is an integrated approach that aims to sustainably balance and optimize human, animal and ecosystem health. Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. Here, we outline such an approach, including the characteristics and components required to overcome barriers and to optimize an integrated One Health surveillance system.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Zoonotic Avian Influenza and Mycobacterium tuberculosis.

Introduction: The Biosafety Research Road Map reviewed the scientific literature on a viral respiratory pathogen, avian influenza virus, and a bacterial respiratory pathogen, Mycobacterium tuberculosis. This project aims at identifying gaps in the data required to conduct evidence-based biorisk assessments, as described in Blacksell et al. One significant gap is the need for definitive data on M. tuberculosis sample aerosolization to guide the selection of engineering controls for diagnostic procedures. Methods: The literature search focused on five areas: routes of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination methods. Results: The available data regarding biosafety knowledge gaps and existing evidence have been collated and presented in Tables 1 and 2. The guidance sources on the appropriate use of biosafety cabinets for specific procedures with M. tuberculosis require clarification. Detecting vulnerabilities in the biorisk assessment for respiratory pathogens is essential to improve and develop laboratory biosafety in local and national systems.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in Human and Veterinary Laboratories.

Introduction: Lack of evidence-based information regarding potential biological risks can result in inappropriate or excessive biosafety and biosecurity risk-reduction strategies. This can cause unnecessary damage and loss to the physical facilities, physical and psychological well-being of laboratory staff, and community trust. A technical working group from the World Organization for Animal Health (WOAH, formerly OIE), World Health Organization (WHO), and Chatham House collaborated on the Biosafety Research Roadmap (BRM) project. The goal of the BRM is the sustainable implementation of evidence-based biorisk management of laboratory activities, particularly in low-resource settings, and the identification of gaps in the current biosafety and biosecurity knowledge base. Methods: A literature search was conducted for the basis of laboratory design and practices for four selected high-priority subgroups of pathogenic agents. Potential gaps in biosafety were focused on five main sections, including the route of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination strategies. Categories representing miscellaneous, respiratory, bioterrorism/zoonotic, and viral hemorrhagic fever pathogens were created within each group were selected for review. Results: Information sheets on the pathogens were developed. Critical gaps in the evidence base for safe sustainable biorisk management were identified. Conclusion: The gap analysis identified areas of applied biosafety research required to support the safety, and the sustainability, of global research programs. Improving the data available for biorisk management decisions for research with high-priority pathogens will contribute significantly to the improvement and development of appropriate and necessary biosafety, biocontainment and biosecurity strategies for each agent.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-SARS-CoV-2.

Introduction: The SARS-CoV-2 virus emerged as a novel virus and is the causative agent of the COVID-19 pandemic. It spreads readily human-to-human through droplets and aerosols. The Biosafety Research Roadmap aims to support the application of laboratory biological risk management by providing an evidence base for biosafety measures. This involves assessing the current biorisk management evidence base, identifying research and capability gaps, and providing recommendations on how an evidence-based approach can support biosafety and biosecurity, including in low-resource settings. Methods: A literature search was conducted to identify potential gaps in biosafety and focused on five main sections, including the route of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination strategies. Results: There are many knowledge gaps related to biosafety and biosecurity due to the SARS-CoV-2 virus's novelty, including infectious dose between variants, personal protective equipment for personnel handling samples while performing rapid diagnostic tests, and laboratory-acquired infections. Detecting vulnerabilities in the biorisk assessment for each agent is essential to contribute to the improvement and development of laboratory biosafety in local and national systems.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Bacillus anthracis and Brucella melitensis.

Introduction: Brucella melitensis and Bacillus anthracis are zoonoses transmitted from animals and animal products. Scientific information is provided in this article to support biosafety precautions necessary to protect laboratory workers and individuals who are potentially exposed to these pathogens in the workplace or other settings, and gaps in information are also reported. There is a lack of information on the appropriate effective concentration for many chemical disinfectants for this agent. Controversies related to B. anthracis include infectious dose for skin and gastrointestinal infections, proper use of personal protective equipment (PPE) during the slaughter of infected animals, and handling of contaminated materials. B. melitensis is reported to have the highest number of laboratory-acquired infections (LAIs) to date in laboratory workers. Methods: A literature search was conducted to identify potential gaps in biosafety and focused on five main sections including the route of inoculation/modes of transmission, infectious dose, LAIs, containment releases, and disinfection and decontamination strategies. Results: Scientific literature currently lacks information on the effective concentration of many chemical disinfectants for this agent and in the variety of matrices where it may be found. Controversies related to B. anthracis include infectious dose for skin and gastrointestinal infections, proper use of PPE during the slaughter of infected animals, and handling contaminated materials. Discussion: Clarified vulnerabilities based on specific scientific evidence will contribute to the prevention of unwanted and unpredictable infections, improving the biosafety processes and procedures for laboratory staff and other professionals such as veterinarians, individuals associated with the agricultural industry, and those working with susceptible wildlife species.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Shigella spp.

Introduction: Shigella bacteria cause shigellosis, a gastrointestinal infection most often acquired from contaminated food or water. Methods: In this review, the general characteristics of Shigella bacteria are described, cases of laboratory-acquired infections (LAIs) are discussed, and evidence gaps in current biosafety practices are identified. Results: LAIs are undoubtedly under-reported. Owing to the low infectious dose, rigorous biosafety level 2 practices are required to prevent LAIs resulting from sample manipulation or contact with infected surfaces. Conclusions: It is recommended that, before laboratory work with Shigella, an evidence-based risk assessment be conducted. Particular emphasis should be placed on personal protective equipment, handwashing, and containment practices for procedures that generate aerosols or droplets.

Decline in radioiodine use but not total thyroidectomy in thyroid cancer patients treated in the United Arab Emirates - A retrospective study.

OBJECTIVES: To assess the trend of clinicopathological features and treatment modalities in patients with thyroid cancer (TC) in the largest oncology center in the United Arab Emirates (UAE). METHODS: A retrospective analysis of patients with TC presenting to a tertiary care hospital in Al Ain, UAE between September 2008 and December 2018 identified using ICD 9 & 10 codes was performed. Data on demographics, histopathology, surgical extent, and use of Radioiodine (RAI) were extracted. Exact logistic and ordinal logistic regressions were performed to analyze the annual trend in features and management of TC, and logistic regression analysis was performed to identify predictors of total thyroidectomy and RAI use. RESULTS: A total of 762 patients were included in the analysis (mean age: 39.6 ± 12.6 years, 45 (60%) women). The majority (92.2%) were diagnosed with papillary thyroid cancer (PTC) and 83.9% had tumor size of <4 cm. All patients underwent surgery (93.8% total thyroidectomy, 6.2% lobectomy) and 77.4% received RAI therapy overall with a significant (p < 0.001) decline from 100% in 2008 to 60% in 2018. In multivariate analysis, nationality, and lymph node (LN) involvement were significant predictors of total thyroidectomy, while nationality, LNs, year of diagnosis, and tumor size significantly predicted RAI use. CONCLUSION: Most patients in our cohort were diagnosed with localized PTC with no significant change in the extent of surgical approach but a substantial decline in RAI therapy administration over time. Nationality and LN involvement were significant predictors of surgical extent and RAI use.

Identification of a novel lineage of Crimean-Congo haemorrhagic fever virus in dromedary camels, United Arab Emirates.

Crimean-Congo haemorrhagic fever virus (CCHFV) is a tick-borne virus causing Crimean-Congo haemorrhagic fever (CCHF), a disease reported to have a high fatality rate in numerous countries. The virus is geographically widespread due to its vector, and numerous wild and domestic animals can develop asymptomatic infection. Serological and limited molecular evidence of CCHFV has previously been reported in Camelus dromedarius (the dromedary, or one-humped camel) in the United Arab Emirates (UAE). In this study, 238 camel samples were screened for CCHFV RNA where 16 camel samples were positive for CCHFV by RT-PCR. Analysis of full-length CCHFV genome sequences revealed a novel lineage in camels from the UAE, and potential reassortment of the M segment of the genome.

Genome Sequencing of a Camelpox Vaccine Reveals Close Similarity to Modified Vaccinia virus Ankara (MVA).

Camelpox is a viral contagious disease of Old-World camelids sustained by Camelpox virus (CMLV). The disease is characterized by mild, local skin or severe systemic infections and may have a major economic impact due to significant losses in terms of morbidity and mortality, weight loss, and low milk yield. Prevention of camelpox is performed by vaccination. In this study, we investigated the composition of a CMLV-based, live-attenuated commercial vaccine using next-generation sequencing (NGS) technology. The results of this analysis revealed genomic sequences of Modified Vaccinia virus Ankara (MVA).

Performance of an Immunochromatographic Test (ICT) in Comparison to Some Commonly Used Serological Tests for the Diagnosis of Brucellosis in Dromedary Camels (Camelus dromedarius).

Serological tests may represent an essential tool for the diagnosis of camel brucellosis; however, concerns arise in the scientific community regarding the direct transposition from cattle and small ruminants without adequate validation. The present study was made to compare four serological tests for the diagnosis of brucellosis in dromedary camels (Camelus dromedarius). In terms of sensitivity, our results show that the Immunochromatographic Test (ICT) shows the higher value of sensitivity, 98.67% (95% Confidence Level (C.L): 94.36%-99.99%), followed by the Fluorescence Polarization Assay (FPA) with 95.05% (95% C.L: 88.23%-99.51%), then the Competitive Enzyme-Linked Immunosorbent Assay (c-ELISA) with 94.94% (95% C.L: 88.25%-99.45%) and, finally, the Rose Bengal Test (RBT) with 68.95% (95% C.L: 56.55%-80.69%), which is the only test showing a significantly lower sensitivity compared to the others. On the other hand, our study revealed no significant difference in terms of specificity between all the tests under study, with a range from 99.06% (95% C.L: 98.34%-99.64%) for the ICT to 99.92% (95% C.L: 99.64%-100%) for the RBT. The ICT was found to be comparable in terms of sensitivity and specificity with the most commonly used tests for camel brucellosis. The results of the present study are of paramount importance for designing surveillance and control measures for brucellosis in camel populations.

Salmonella enterica and Theileria co-infection in dromedary camels (Camelus dromedarius) in UAE.

Background: Despite a steady increase in camel husbandry worldwide, pathology of camel diseases is still relatively under-investigated. Clinical hematuria is generally indicative of either acute or chronic urogenital inflammations, traumatic calculous injuries, cancers, corrosive poisonings. Infectious agents are not typically implicated in urinary tract infection of camels. Aim: This study aims to explore possible causes in camels clinically suffered from acute febrile disease with severe hematuria. Methods: To achieve aims of the study culturing of urine samples, microscopic examination for detection of blood parasites, phenotypic and genotypic characterization for the identification of isolated bacteria were followed. Results: Conventional bacteriology enabled identification of Salmonella enterica subsp. enterica serovar typhimurium which further genotyped by 16S rRNA gene sequencing. Microscopic examination of Giemsa stained blood smears from both infected dromedary camels revealed the presence of pleomorphic Theileria piroplasms. The results suggest that the clinical symptoms were as coinfection induced by salmonellosis and theileriosis. Conclusion: Given these remarkable findings, further research should aim to better characterize the opportunistic pathogens associated with camel theileriosis, as well as to determine other possible infectious agents of the camel urinary tract.